臺灣博碩士論文加值系統

表面電漿共振(Surface Plasmon Resonance, SPR)現象，被發現已經有近一百年的歷史，而近幾年來，隨著生物醫學的發展，這項技述更是被廣泛的應用在生物檢測的範圍內，由於它對不同折射率的待測物有高靈敏度的特性，因此，常常被用來作生物醫學檢測。常見的表面電漿共振量測方式有四種，角度調制、波長調制、強度調制以及相位調制，其中以相位靈敏度最高，因最大的相位變化發生在SPR曲線最窄處，也是探測電場向量最大處，所以為了取得反射光相位資訊，本論文使用低同調干涉的表面電漿感測器架構來檢測微小核醣核酸的濃度變化。
在本論文中，通訊波段寬頻譜光源作為我們低同調干涉技術的主要來源，接著利用兩級的Mach–Zehnder干涉儀，作為此實驗架構的主體，並結合表面電漿共振現象，達到生物醫學感測目的，也因為使用兩級Mach–Zehnder干涉儀，成功解決一級Mach–Zehnder干涉儀沒有基準點可以做為濃度變化依據的問題，最後透過電腦分析不同濃度待測物之實驗結果。本實驗生醫量測在無探針(Probe)時，濃度變化的靈敏度為0.0606 (μm/(μg/mL))，而有探針的濃度變化靈敏度為0.088 (μm/(μg/mL))，從此可見靈敏度上升了1.45倍，解析度也相對增加了1.45倍，此說明了固定化探針可有效抓取標的物(miRNA)，也有更好的解析度。

With the biomedical technique development, surface plasmon resonance (SPR), which phenomenon has been found for nearly a hundred years, is widely utilized in biological detection due to its high sensitivity. There are four kinds of SPR characterizations - angle, wavelength, intensity and phase modulation. Among them, the phase modulation demonstrates the highest sensitivity because the maximum phase change occurs in the SPR curve dip where the largest electric field is happening. In order to retrieve the reflected light phase information, the low coherence interferometry based SPR sensor is utilized to detect various concentrations of microRNA in this thesis.
A superluminescent emitting diode with the center wavelength of 1550 nm is utilized as the light source to demonstrate low coherence interferometry in two-stage Mach-Zehnder interferometer where the SPR is built within one of two stages. The advantage for two-stage Mach-Zehnder interferometer is that the bench mark can be taken as a reference point during biosensing. A DNA sequence antisensed from microRNA DNA utilized as the prober and the sensitivity and resolution demonstrate as 0.088 (μm/(μg/mL)) and 4.5399×10^(-7), respectively.

目錄
圖目錄 VI
表目錄 IX
第一章 緒論 1
1.1 研究背景 1
1.2 研究目的 2
1.3 研究之重要性 3
1.4 論文架構 4
第二章 文獻探討 5
2.1 表面電漿波原理 5
2.1.1 表面電漿波形成 5
2.1.2激發表面電漿條件與稜鏡耦合 12
2.2 Mazh-Zehnder干涉儀 15
2.3光纖低同調光學干涉 17
2.4表面電漿共振生物感測器 22
2.5國內外SPR干涉之生物感測器 24
第三章 研究與模擬方法 31
3.1 金薄膜厚度設計 31
3.1.1 Kretschman結構下系統反射率 31
3.1.2 金薄膜厚度模擬與製程 34
3.2 SPR金薄膜之製程 36
3.2.1 使用設備 36
3.2.2 製程步驟 37
第四章 實驗步驟與結果分析 39
4.1 實驗架構 39
4.2實驗步驟 41
4.2.1待測物的準備 41
4.2.2 DNA固定化程序 43
4.2.3 入射角度之控制 46
4.2.4 OFLCI SPR實驗步驟 49
4.3量測結果與討論 52
4.3.1 葡萄醣量測結果 52
4.3.2 使用probe之miRNA DNA 量測結果 54
4.3.3未使用probe的miRNA DNA量測結果 56
4.3.4 miRNA檢體量測結果 58
4.3.5 干涉驗證 60
4.3.6 模擬與實驗解析度分析 63
第五章 結論與未來展望 67
5.1 結論 67
5.2未來展望 68
參考文獻 69

[1] R. Wood, "On a Remarkable Case of Uneven Distribution of Light in a Diffraction Grating Spectrum", Proceedings of the Physical Society of London, vol. 18, no. 1, pp. 269-275, 1902.
[2] U. Fano, "The Theory of Anomalous Diffraction Gratings and of Quasi-Stationary Waves on Metallic Surfaces (Sommerfeld’s Waves)", Journal of the Optical Society of America, vol. 31, no. 3, p. 213, 1941.
[3] R. Ritchie, "Plasma Losses by Fast Electrons in Thin Films", Physical Review, vol. 106, no. 5, pp. 874-881, 1957.
[4] E. Kretschmann and H. Raether, "Notizen: Radiative Decay of Non Radiative Surface Plasmons Excited by Light", Zeitschrift für Naturforschung A, vol. 23, no. 12, 1968.
[5] A. Otto, "Excitation of nonradiative surface plasma waves in silver by the method of frustrated total reflection", Zeitschrift für Physik A Hadrons and nuclei, vol. 216, no. 4, pp. 398-410, 1968.
[6] K. O'Donnell, E. Wentzel, K. Zeller, C. Dang and J. Mendell, "c-Myc-regulated microRNAs modulate E2F1 expression", Nature, vol. 435, no. 7043, pp. 839-843, 2005.
[7] R. Lee, J. Hench and G. Ruvkun, "Regulation of C. elegans DAF-16 and its human ortholog FKHRL1 by the daf-2 insulin-like signaling pathway", Current Biology, vol. 11, no. 24, pp. 1950-1957, 2001.
[8] P. Xu, S. Vernooy, M. Guo and B. Hay, "The Drosophila MicroRNA Mir-14 Suppresses Cell Death and Is Required for Normal Fat Metabolism", Current Biology, vol. 13, no. 9, pp. 790-795, 2003.
[9] J. DOSTIE, "Numerous microRNPs in neuronal cells containing novel microRNAs", RNA, vol. 9, no. 2, pp. 180-186, 2003.
[10] Y. Xu and C. Quinn, "Transition between synaptic branch formation and synaptogenesis is regulated by the lin-4 microRNA", Developmental Biology, vol. 420, no. 1, pp. 60-66, 2016.
[11] 吳民耀與劉威志， “表面電漿子理論與模擬，” 物理雙月刊，廿八卷二期，pp. 486-496，2006
[12] 邱國斌與蔡定平， “金屬表面電漿簡介，” 物理雙月刊，廿八卷二期，pp. 472-485，2006。
[13] J. Homola, "Surface Plasmon resonance sensors for detection of chemical and biological species," Chemical Reviews, vol. 108, no. 2, pp. 462–493, Feb. 2008.
[14] E. Krestschmann, “The determination of the optical constants of metals by excitation of surface plasmons,” Z. Physik, vol. 241, pp. 313, 1971.
[15] C. Lawson and R. Michael, "Fiber optic low-coherence interferometry for non-invasive silicon wafer characterization", Journal of Crystal Growth, vol. 137, no. 1-2, pp. 37-40, 1994.
[16] 游輝智，”光學低同調干涉技術系統的建構與應用”，國立台灣科技大學電子工程所，2008。
[17] 吳宗正， “生物感測器，” 生物技術，九州出版社，第十八章，pp. 24-262，1996。
[18] A. Hulanicki, “Chemical sensors definitions and classification,” Pure and Applied Chemistry, vol. 63, no. 9, pp. 1247-1250, 1991.
[19] S. Zeng, K. Yong, I. Roy, X. Dinh, X. Yu and F. Luan, "A Review on Functionalized Gold Nanoparticles for Biosensing Applications", Plasmonics, vol. 6, no. 3, pp. 491-506, 2011.
[20] C. Wu and M. Pao, "Sensitivity-tunable optical sensors based on surface plasmon resonance and phase detection", Optics Express, vol. 12, no. 15, p. 3509, 2004.
[21] M. Kashif, A. Bakar, N. Arsad and S. Shaari, "Development of Phase Detection Schemes Based on Surface Plasmon Resonance Using Interferometry", Sensors, vol. 14, no. 9, pp. 15914-15938, 2014.
[22] A. Kabashin and P. Nikitin, "Interferometer based on a surface-plasmon resonance for sensor applications", Quantum Electronics, vol. 27, no. 7, pp. 653-654, 1997.
[23] 林萱, “利用相位式表面電漿共振系統 檢測免疫球蛋白鍵結之應用分析,” 國立中央大學光電科學與工程學系研究所碩士論文, 2012
[24] 王雅榕,“改善光相位解析式表面電漿共振生物感測器之靈敏度及表面電漿共振影像系統之發展,” 國立陽明大學生醫光電研究所碩士論文, 2009
[25] 陳威州,“以角度偏向放大器結合表面電漿共振外差干涉術作微小位移量測,” 國立虎尾科技大學光電與材料科技研究所碩士論文, 2014
[26] Y. Huang, H. Ho, S. Kong and A. Kabashin, "Phase-sensitive surface plasmon resonance biosensors: methodology, instrumentation and applications", Annalen der Physik, vol. 524, no. 11, pp. 637-662, 2012.
[27] J. Homola, “Springer series on chemical sensors and biosensors,” Springer, vol. 4, pp. 3-44, 2006.
[28] A. Rakić, A. Djurišić, J. Elazar and M. Majewski, "Optical properties of metallic films for vertical-cavity optoelectronic devices", Applied Optics, vol. 37, no. 22, p. 5271, 1998.
[29] P. B. Johnson and R. W. Christy, “Optical Constants of the Noble Metals,” Physical Review B, vol. 6, pp. 4370-4379, 1972.
[30] SCHOTT Taiwan Ltd., optical glass data sheets, 2015.